The paradox of modern times is that while we are able to extend life, our brains do not always keep up in maintaining performance. Society is aging, and with age the risk of neurodegenerative diseases increases. Forecasts are alarming – the number of patients with Alzheimer’s disease is expected to double by 2050. “This is a problem of our civilization, growing at an exponential rate,” says Dr Agnieszka Krzyżosiak, leader of the Neurodegeneration Mechanisms Research Group at Łukasiewicz – PORT.
Pathological proteins in neurons
Neurodegenerative diseases remain practically incurable. Despite the optimism offered by modern approaches such as therapeutic antibodies or gene therapies, medicine still lacks a ready solution. This is why understanding the mechanisms by which these diseases develop is so important.
“In the vast majority of cases these are not hereditary diseases, and the main risk factor is age,” explains the researcher. A common denominator for many of these conditions turns out to be the accumulation of pathological proteins in nerve cells.
In a healthy cell, a specialized protein quality control system operates – defective proteins are eliminated, and the cell maintains balance. In sick cells, this system fails.
“Proteostasis is disrupted, and pathological proteins accumulate in the form of toxic aggregates that lead to neuronal death,” says Dr Krzyżosiak.
This mechanism has become the core of the research at Łukasiewicz – PORT.
“If we manage to strengthen the protein quality control system and stop their pathological accumulation, we will be able to slow down the progression of neurodegenerative diseases,” emphasizes the scientist. Her team is also looking for biomarkers – early warning signals in the patient’s body.
“We want to detect these diseases as early as possible, analyze blood or cerebrospinal fluid samples, and combine clinical data with laboratory observations.”
Cell reprogramming
Modern science is providing more and more tools to achieve this.
“We focus on modeling diseases in human cells,” says the researcher. In her laboratory, models based on reprogramming patient fibroblasts into neurons are being developed.
“This is a breakthrough approach because the reprogrammed cells retain the patient’s age. And age is the main risk factor.”
This allows scientists to observe disease processes in conditions much closer to reality than classical animal models. Cells taken from patients retain the human genetic background, and also “remember” their age and the transcriptional and epigenetic changes related to aging — enabling researchers to study how the disease truly develops in the human brain.
The experience of Dr Krzyżosiak shows that laboratory discoveries can lead to real therapies. During her fellowship in Cambridge, her team discovered a chemical compound that supports the cell’s natural defense mechanisms and helps alleviate symptoms of neurodegenerative diseases.
“What we started from scratch in the lab is now in Phase II clinical trials for ALS,” she says proudly.
However, the path from discovery to therapy requires more than science alone.
“Commercializing research is always a huge challenge. My experience in Cambridge showed me how important networking and a supportive biotech environment are. Thanks to this, our research results can be translated into practical applications,” says Dr Krzyżosiak, who has always been drawn to translational science.
The researcher emphasizes that progress in this field is impossible without the participation of patients and society.
“Medical data or biological samples are extremely valuable material. They help us better understand diseases, and everything is done fully anonymously.”
Conversations about brain health
According to Dr Krzyżosiak, each of us has an impact on the condition of our brain:
“Lifestyle matters. An unhealthy diet, lack of exercise or overstimulation burden neurons. Intellectual activity in older adults, even in the form of solving crosswords, helps maintain brain plasticity.”
In a few days, one of the most important events for nervous system researchers will begin in Wrocław – the Congress of the Polish Society for Neuroscience (PTBUN). Dr Agnieszka Krzyżosiak is enthusiastic about the upcoming event:
“The scientific level of the congress is very high, it allows researchers from different fields to meet. Multidisciplinarity is the key if we really want to understand disease mechanisms and develop effective therapies.”
She also points out the open panel dedicated to aging and dementia —
“Neurosociety: the senior at the center of medical innovation”, held on 2 September, 15:00–16:45, at the Wrocław University of Science and Technology Congress Center (Janiszewskiego 8). Residents of Lower Silesia, seniors, and their families will have the opportunity to discuss dementia with city officials, doctors, and researchers. Dr Krzyżosiak emphasizes:
“It’s important that these conversations involve not only scientists but also patients and society, because aging is an issue that concerns us all.”
